Standardized Grass Pollen, Fescue, Meadow: Package Insert and Label Information

STANDARDIZED GRASS POLLEN, FESCUE, MEADOW- festuca pratensis pollen injection, solution
STANDARDIZED GRASS POLLEN, REDTOP- agrostis gigantea pollen injection, solution
STANDARDIZED GRASS POLLEN, ORCHARD GRASS- dactylis glomerata pollen injection, solution
STANDARDIZED GRASS POLLEN, BERMUDA GRASS- cynodon dactylon pollen injection, solution
STANDARDIZED GRASS POLLEN, TIMOTHY- phleum pratense pollen injection, solution
STANDARDIZED GRASS POLLEN, SWEET VERNAL GRASS- anthoxanthum odoratum pollen injection, solution
STANDARDIZED GRASS POLLEN, RYEGRASS- lolium perenne pollen injection, solution
STANDARDIZED GRASS POLLEN, BLUEGRASS, KENTUCKY JUNE- poa pratensis pollen injection, solution
Jubilant HollisterStier LLC

WARNINGS

This product is intended for use only by licensed medical personnel experienced in administering allergenic extracts and trained to provide immediate emergency treatment in the event of a life-threatening reaction.

Allergenic extracts may potentially elicit a severe life-threatening systemic reaction, rarely resulting in death 1. Therefore, emergency measures and personnel trained in their use must be available immediately in the event of such a reaction. Patients should be instructed to recognize adverse reaction symptoms and cautioned to contact the physician’s office if symptoms occur. See ADVERSE REACTION, Section 3, of this insert for information regarding adverse event reporting.
Standardized glycerinated extracts may differ in potency from regular extracts and therefore, are not directly interchangeable with non-standardized extracts, or other manufacturers’ products.
Note: BAU/mL Standardized grass pollens are not interchangeable with any other grass pollen products. This product should never be injected intravenously. Patients with cardiovascular diseases or pulmonary diseases such as symptomatic unstable, steroid-dependent asthma, and/or those who are receiving cardiovascular drugs such as beta blockers, may be at higher risk for severe adverse reactions. These patients may also be more refractory to the normal allergy treatment regimen. Patients should be treated only if the benefit of treatment outweighs the risks.1
Refer also to the CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS and OVERDOSE Sections for further discussion.

DESCRIPTION

The grass pollens available in standardized form are: Bermuda Grass (Cynodon dactylon), Orchard Grass (Dactylis glomerata), Perennial Ryegrass (Lolium perenne), Timothy Grass (Phleum pratense), Redtop Grass (Agrostis alba), Kentucky Bluegrass (Poa pratensis), Meadow Fescue (Festuca elatior), and Sweet Vernalgrass (Anthoxanthum odoratum). The pollen extracts are intended for subcutaneous injection for immunotherapy; and intradermal and prick or puncture for diagnosis. Pollen extracts are sterile solutions containing the extractables of pollens, 0.5% Sodium Chloride, 0.275% Sodium Bicarbonate, and 50% Glycerin by volume as a preservative. Sterile, diluted Standardized Grass Pollen Extracts available for intradermal testing contain 0.9% sodium chloride, not more than 0.5% glycerin by volume, 0.03% sodium bicarbonate, and 0.4% phenol as a preservative. Source material for the extracts is collected using techniques such as water set or vacuuming. Source material for allergenic extracts contains no more than a total of 1% of detectable foreign materials (99% pollen purity). Note: BAU/mL Standardized grass pollens are not interchangeable with any other grass pollen products.

Product Concentration:
1. Bioequivalent Allergy Units. These allergenic extracts are labeled in Bioequivalent Allergy Units/mL (BAU/mL) based on their comparison (by ELISA Competition) to Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA) Reference Preparations.2 The FDA reference extracts have been assigned Bioequivalent Allergy Units based on the CBER ID50 EAL method.5 Briefly, highly sensitive patients are skin tested to the reference preparation using an intradermal technique employing 3-fold extract dilutions. Depending on the dilution which elicits a summation of erythema diameter of 50mm (D50 ), Bioequivalent Allergy Units are assigned as follows:

BAU/mL Intradermal Mean Dilution D50
1000,000 1:5,000,000 13-14.9
10,000 1:500,000 11-12.9
1,000 1:50,000 9-10.9

The vial potency of Mixtures of Standardized Grasses is calculated by summation of the BAU/mL values of the components of the ingredient list which expresses the potency of each component per mL of the mixture.

2. Concentrate.
a. Concentrate label terminology applies to allergenic extract Custom Mixtures where the individual allergens being combined vary in strength or the designation of strength.

e.g. Concentrate
50% Short Ragweed 1:20 w/v
25% Kentucky Bluegrass 100,000 BAU/mL
25% Std. Mite D. farinae 10,000 AU/mL

Should the physician choose to calculate the actual strength of each component in the “Concentrate” mixture, the following formulation may be used:

Actual Allergen Strength in Concentrate Mixture = Allergen Manufacturing Strength x Allergen in Formulation (by volume or parts)

b. In the list of components portion of the product label for Stock Mixtures Containing Standardized Grasses , the potency of each component is calculated to express the potency of each component per 1 mL of the mixture. Vial potency is expressed as concentrate, or as a volume/volume dilution of concentrate.

CLINICAL PHARMACOLOGY

20

The mechanisms by which hyposensitization is achieved are not completely understood. It has been shown that repeated injections of appropriate allergenic extracts will ameliorate the intensity of allergic symptoms upon contact with the allergen.6, 7, 8, 9 Clinical studies which address the efficacy of immunotherapy are available. The allergens which have been studied are cat, mite, and some pollen extracts.10, 11, 12, 13, 14, 15
IgE antibodies bound to receptors on mast cell membranes are required for the allergic reaction, and their level is probably related to serum IgE concentrations. Immunotherapy has been associated with decreased levels of IgE, and also with increases in allergen specific IgG “blocking” antibody.
The histamine release response of circulating basophils to a specific allergen is reduced in some patients by immunotherapy, but the mechanism of this change is not yet clear.
The relationships among changes in blocking antibody, reaginic antibody, and mediator-releasing cells, and successful immunotherapy need study and clarification.
The CBER has evaluated the potency of eight grass pollen extract reference preparations and assigned potency units (BAU/mL) to each.5 The CBER clinical results follow in Table 1. Puncture data were obtained using a bifurcated needle.
Table 1
PUNCTURE AND INTRADERMAL DATA WITH CBER GRASS REFERENCES 3A. Puncture Data with 10,000 BAU/mL Grass Extracts

Sum of Erythema (mm) Sum of Wheal (mm)
Reference Pollen N Mean Range Mean Range
Bermuda Grass — Cynodon dactylon 15 90.3 43-123 15.7 7-31
Kentucky Bluegrass (June) — Poa pratensis 15 77.3 47-107 15.9 6-28
Meadow Fescue — Festuca elatior 15 81.1 57-115 11.9 7-22
Orchard Grass — Dactylis glomerata 15 84.3 57-111 14.1 9-19
Perennial Ryegrass — Lolium perenne 15 92.3 73-135 17.5 6-36
Redtop — Agrostis gigantea (alba) 15 77.1 42-98 14.1 8-19
Sweet Vernalgrass — Anthoxanthum odoratum 15 81.2 28-123 15.7 8-30
Timothy — Phleum pratense 15 88.3 51-109 16.9 8-40

B. Intradermal Dose of CBER Grass References for 50mm Sum of Erythema (BAU50 )

Reference Pollen Mean BAU50 /mL Range
Bermuda Grass — Cynodon dactylon 0.02 0.4-0.0003
Kentucky Bluegrass (June) — Poa pratensis 0.02 0.1-0.004
Meadow Fescue — Festuca elatior 0.02 0.9-0.002
Orchard Grass — Dactylis glomerata 0.02 1.9-0.002
Perennial Ryegrass — Lolium Perenne 0.02 0.7-0.002
Redtop — Agrostis gigantea (alba) 0.02 0.8-0.004
Sweet Vernalgrass — Anthoxanthum odoratum 0.02 1.0-0.002
Timothy — Phleum pratense 0.02 0.6-0.002

TABLE 2

RELATIVE POTENCY OF PREVIOUSLY MANUFACTURED AND DISTRIBUTED NON-STANDARDIZED GRASSES TO CBER REFERENCE STANDARDSGlycerinated (1:20 w/v) and Non-Glycerinated Pollen Extracts (1:10 w/v)

# of Jubilant HollisterStier LLC Lots Relative to the CBER Reference*
Pollen # of Lots Tested Less than Equal to Greater Than Calculated BAU/mL Range** (Rounded to the nearest 000)
Orchard Grass 20 2 13 5 66,000 — 242,000
Perennial Ryegrass 17 5 12 0 25,000 — 127,000
Sweet Vernalgrass 13 1 12 0 73,000 — 110,000
Kentucky Bluegrass 21 8 12 1 32,000 — 145,000
Redtop 20 5 6 9 13,000 — 402,000
Meadow Fescue 21 0 1 20 128,000 — 948,000
Bermuda Grass 22 3 13 6 6,000 — 28,000
Timothy 19 11 6 2 43,000 — 176,000

*All CBER reference extracts contain 100,000 BAU/mL except Bermuda Grass which contains 10,000 BAU/mL.

**BAU/mL ranges between 69,990 and 143,100 are considered equivalent to the CBER 100,000 BAU/mL Standard, and between 6,990 and 14,310 for the CBER 10,000 BAU/mL Standard when assays are done in triplicate.

INDICATIONS AND USAGE

16, 17, 18, 20

Standardized glycerinated allergenic extracts in potencies of 10,000 BAU/mL and 100,000 BAU/mL are indicated for use in diagnosis and immunotherapy of patients presenting symptoms of allergy (hay fever, rhinitis, etc.) to specific grass pollens. Concentrated extracts must be diluted prior to use in intradermal testing and immunotherapy. The selection of allergenic extracts to be used should be based on a thorough and carefully taken history of hypersensitivity, and confirmed by skin testing. 27, 28 10,000 BAU/mL dose form should be used initially for percutaneous testing. If negative, the 100,000 BAU/mL dose can be used.
The use of mixed or unrelated antigens for skin testing is not recommended since, in the case of a positive reaction, it does not indicate which component of the mix is responsible for the reaction, while, in the case of a negative reaction, it fails to indicate whether the individual antigens at full concentration would give a positive reaction. Utilization of such mixes for compounding a treatment may result, in the former case, in administering unnecessary antigens and, in the latter case, in the omission of a needed allergen.
Allergens to which a patient is extremely sensitive should not be included in treatment mixes with allergens to which there is much less sensitivity, but should be administered separately. This allows individualized and better control of dosage increases, including adjustments in dosage becoming necessary after severe reactions which may occur to the highly reactive allergen. Note: BAU/mL Standardized grass pollens are not interchangeable with any other grass pollen products.

CONTRAINDICATIONS

There are no known absolute contraindications to immunotherapy. See PRECAUTIONS for pregnancy risks.
Patients with cardiovascular diseases or pulmonary diseases such as symptomatic unstable, steroid-dependent asthma, and/or those who are receiving cardiovascular drugs such as beta blockers, may be at higher risk for severe adverse reactions. These patients may also be more refractory to the normal allergy treatment regimen. Patients should be treated only if the benefit of treatment outweighs the risks.1
Any injections, including immunotherapy, should be avoided in patients with a bleeding tendency.
Since there are differences of opinion concerning the possibility of routine immunizations exacerbating autoimmune diseases, immunotherapy should be given cautiously to patients with autoimmune diseases, and only if the risk from exposure to the allergen is greater than the risk of exacerbating the autoimmune process.

WARNINGS

See WARNINGS at the beginning of this instruction sheet.

Allergenic extract should be temporarily withheld from patients or the dose adjusted downward if any of the following conditions exist: (1) severe symptoms of rhinitis and/or asthma; (2) infection or flu accompanied by fever; or (3) exposure to excessive amounts of clinically relevant allergen prior to a scheduled injection. Do not start immunotherapy during a period of symptoms due to exposure. Since the individual components of the extract are those to which the patient is allergic, and to which he or she will be exposed, typical allergic symptoms may follow shortly after the injection, particularly when the antigen load from exposure plus the injected antigen exceeds the patient’s antigen tolerance. (4) Any evidence of a local or generalized reaction requires a reduction in dosage during the initial stages of immunotherapy, as well as during maintenance therapy.
THE CONCENTRATE SHOULD NOT BE INJECTED AT ANY TIME UNLESS TOLERANCE HAS BEEN ESTABLISHED. DILUTE CONCENTRATED EXTRACTS WITH STERILE ALBUMIN SALINE WITH PHENOL (0.4%) FOR INTRADERMAL TESTING.
INJECTIONS SHOULD NEVER BE GIVEN INTRAVENOUSLY. Subcutaneous injection is recommended. Intracutaneous or intramuscular injections may produce large local reactions or be excessively painful.
AFTER INSERTING NEEDLE SUBCUTANEOUSLY, BUT BEFORE INJECTING, ALWAYS WITHDRAW THE PLUNGER SLIGHTLY. IF BLOOD APPEARS IN THE SYRINGE, CHANGE NEEDLE AND GIVE THE INJECTION IN ANOTHER SITE.

IF CHANGING TO A DIFFERENT LOT OF STANDARDIZED EXTRACT: Even though it is the same formula and concentration, the first dose of the new extract should not exceed 25% to 50% of the last administered dose from the previous extract.

IF THE STANDARDIZED EXTRACT PREVIOUSLY USED WAS FROM ANOTHER MANUFACTURER: Since manufacturing processes and sources of raw materials differ among manufacturers, the interchangeability of extracts from different manufacturers cannot be insured. The starting dose of the standardized glycerinated extract therefore should be greatly decreased even though the extract is the same formula and dilution. Initiate therapy as though patient had not been receiving immunotherapy, or determine initial dose by skin test using serial dilutions of the extract. In highly sensitive individuals, the skin test method may be preferable. See DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS Sections.
IF A PROLONGED PERIOD OF TIME HAS ELAPSED SINCE THE LAST INJECTION: Patients may lose tolerance for allergen injections during prolonged periods between doses. The duration of tolerance is an individual characteristic and varies from patient to patient. In general, the longer the lapse in the injection schedule, the greater dose reduction required. If the interval since last dose is over four weeks, perform skin tests to determine starting dose.
IF THE PREVIOUS EXTRACT WAS OUTDATED: The dating period for allergenic extracts indicates the time that they can be expected to remain potent under refrigerated storage conditions (2°- 8°C). During the storage of extracts, even under ideal conditions, some loss of potency occurs. For this reason, extracts should not be used beyond their expiration date. If a patient has been receiving injections of an outdated extract, he may experience excessive local or systemic reactions when changed to a new, and possibly more potent extract. In general, the longer the material has been outdated, the greater the dose reduction necessary for the fresh extract.
IF THE PREVIOUS EXTRACT WAS NON-STANDARDIZED: Standardized extracts differ in potency from non-standardized extracts. Use Table 2 for guidance in selecting dose for switching. To confirm dose selected, side-by-side skin testing of new and old extracts can be carried out. (See CLINICAL PHARMACOLOGY, Table 2.) Initiate therapy as though the patient had not been receiving immunotherapy, or determine initial dose by skin test using serial dilutions of the extract. See PRECAUTIONS and DOSAGE AND ADMINISTRATION Sections below.
IF ANY OTHER CHANGES HAVE BEEN MADE IN THE EXTRACT CONCENTRATE FORMULA: Changes other than those listed above may include situations such as a redistribution of component parts or percentages, a difference in extracting fluid (i.e., change from non-glycerin extracts to 50% glycerin extracts), combining two or more stock concentrates, or any other change.
It should be recognized that any change in formula can affect a patient’s tolerance of the treatment. The usual 1/2 of the previous dose for a new extract may produce an adverse reaction; extra dilutions are recommended whenever starting a revised formula. The greater the change, the greater the number of dilutions required.

DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.

As the leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. Our material is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2021. All Rights Reserved.